The dextrorotary (+)- or d- enantiomer is (1S,2S)-pseudoephedrine, whereas the levorotating (−)- or l- form is (1R,2R)-pseudoephedrine.

In the outdated d/l system (+)-pseudoephedrine is also referred to as l-pseudoephedrine and (−)-pseudoephedrine as d-pseudoephedrine (in the Fisher projection then the phenyl ring is drawn at bottom).[4][5]

Often the d/l system (with small caps) and the d/l system (with lower-case) are confused. The result is that the dextrorotary d-pseudoephedrine is wrongly named d-pseudoephedrine and the levorotary l-ephedrine (the diastereomer) wrongly l-ephedrine.

The IUPAC names of the two enantiomers are (1S,2S)- respectively (1R,2R)-2-methylamino-1-phenylpropan-1-ol. Synonyms for both are psi-ephedrine and threo-ephedrine.

Although pseudoephedrine occurs naturally as an alkaloid in certain plant species (for example, as a constituent of extracts from the Ephedra species, also known as ma huang, in which it occurs together with other isomers of ephedrine), the majority of pseudoephedrine produced for commercial use is derived from yeastfermentation of dextrose in the presence of benzaldehyde. In this process, specialized strains of yeast (typically a variety of Candida utilis or Saccharomyces cerevisiae) are added to large vats containing water, dextrose and the enzyme pyruvate decarboxylase (such as found in beets and other plants). After the yeast has begun fermenting the dextrose, the benzaldehyde is added to the vats, and in this environment the yeast converts the ingredients to the precursor l-phenylacetylcarbinol (L-PAC). L-PAC is then chemically converted to pseudoephedrine via reductive amination.[7]

Pseudoephedrine acts on α- and β2-adrenergic receptors, to cause vasoconstriction and relaxation of smooth muscle in the bronchi, respectively.[9][10] α-adrenergic receptors are located on the muscles lining the walls of blood vessels. When these receptors are activated, the muscles contract, causing the blood vessels to constrict (vasoconstriction). The constricted blood vessels now allow less fluid to leave the blood vessels and enter the nose, throat and sinus linings, which results in decreased inflammation of nasal membranes, as well as decreased mucus production. Thus, by constriction of blood vessels, mainly those located in the nasal passages, pseudoephedrine causes a decrease in the symptoms of nasal congestion. Activation of β2-adrenergic receptors produces relaxation of smooth muscle of the bronchi,[9] causing bronchial dilation and in turn decreasing congestion (although not fluid) and difficulty breathing.

Pseudoephedrine can be used either as oral or as topical decongestant. However, due to its stimulating qualities, the topical nasal preparation is more likely to cause adverse effects, including urinary retention.[12][13] According to one study, pseudoephedrine may show effectiveness as an antitussive drug (suppression of cough).[14]

There have been reports of off-label uses of pseudoephedrine for its stimulant properties. Long-distance truck drivers and athletes, for example, have reportedly used pseudoephedrine as a stimulant to increase their state of alertness/awareness.[citation needed]

Pseudoephedrine was on the IOC's banned substances list until 2004, when the World Anti-Doping Agency (WADA) list replaced the IOC list. Although WADA initially only monitored pseudoephedrine, it is once again on the banned list starting January 1, 2010.[26]

Pseudoephedrine is excreted through urine, and concentration in urine of this drug shows a large inter-individual spread; that is, the same dose can give a vast difference in urine concentration for different individuals.[27] Pseudoephedrine is approved to be taken up to 240 mg per day. In seven healthy male subjects this dose yielded a urine concentration range of 62.8 to 294.4 microgram per milliliter (µg/ml) with mean ± standard deviation 149 ± 72 µg/ml.[28] Thus, normal dosage of 240 mg pseudoephedrine per day can result in urine concentration levels exceeding the limit of 150 µg/ml set by WADA for about half of all users.[29] Furthermore, hydration status does not affect urinary concentration of pseudoephedrine.[30]

In February 2000, Elena Berezhnaya and Anton Sikharulidze won gold at the 2000 European Figure Skating Championships but were stripped of their medals after Berezhnaya tested positive. This resulted in a three-month disqualification from the date of the test, and the medal being stripped.[32] She stated that she had taken cold medication approved by a doctor but had failed to inform the ISU as required.[33] The pair missed the World Championships that year as a result of the disqualification.

Romanian gymnast Andreea Răducan was stripped of her gold medal at the 2000 Sydney Olympics after testing positive. She took two pills given to her by the team coach for a cold. Although she was stripped of the overall gold medal, she kept her other medals, and, unlike in most other doping cases, was not banned from competing again; only the team doctor was banned for a number of years. Ion Ţiriac, the president of the Romanian Olympic Committee, resigned over the scandal.[34][35]

In the 2014 Sochi Olympics the team Sweden and Washington Capitals ice hockey player Nicklas Bäckström was prevented from playing in the final for usage of pseudoephedrine. Bäckström claimed he was using it as allergy medication.[37] In March 2014, the IOC Disciplinary Commission decided that Bäckström would be awarded the silver medal.[38] In January 2015 Bäckström, the IOC, WADA and the IIHF agreed to a settlement in which he accepted a reprimand but was cleared of attempting to enhance his performance.[39]

Pseudoephedrine may be quantitated in blood, plasma or urine to monitor any possible performance-enhancing use by athletes, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Many commercial immunoassay screening tests directed at the amphetamines cross-react appreciably with pseudoephedrine, but chromatographic techniques can easily distinguish pseudoephedrine from other phenethylamine derivatives. Blood or plasma pseudoephedrine concentrations are typically in the 50–300 µg/l range in persons taking the drug therapeutically, 500–3000 µg/l in abusers or poisoned patients and 10–70 mg/l in cases of acute fatal overdosage.[40][41]

Illicit diversion of pseudoephedrine in Australia has caused significant changes to the way the products are regulated. As of 2006[update], all products containing pseudoephedrine have been rescheduled as either "Pharmacist Only Medicines" (Schedule 3) or "Prescription Only Medicines" (Schedule 4), depending on the amount of pseudoephedrine in the product. A Pharmacist Only Medicine may only be sold to the public if a pharmacist is directly involved in the transaction. These medicines must be kept behind the counter, away from public access.

Pharmacists are also encouraged (and in some states required) to log purchases with the online database Project STOP.[42] This system aims to prevent individuals from purchasing small quantities of pseudoephedrine from many different pharmacies.

As a result, many pharmacies no longer stock Sudafed, the common brand of pseudoephedrine cold/sinus tablets, opting instead to sell Sudafed PE, a phenylephrine product which has not been proven effective in clinical trials.[22][43][44]

Health Canada has investigated the risks and benefits of pseudoephedrine and ephedrine/ephedra. Near the end of the study, Health Canada issued a warning on their website stating that those who are under the age of 12, or who have heart disease and may suffer from strokes, should avoid taking pseudoephedrine and ephedrine. Also, they warned that everyone should avoid taking ephedrine or pseudoephrine with other stimulants like caffeine. They also banned all products that contain both ephedrine (or pseudoephedrine) and caffeine.[45]

Products whose only medicinal ingredient is pseudoephedrine must be kept behind the pharmacy counter. Products containing pseudoephedrine along with other medicinal ingredients may be displayed on store shelves but may be sold only in a pharmacy when a pharmacist is present.[46][47]

In New Zealand, pseudoephedrine is currently classified as a Class B Part II controlled drug in the Misuse of Drugs Act 1975, making it illegal to supply or possess except on prescription.[51][52].

Pseudoephedrine, ephedrine, and any product containing these substances, e.g. cold and flu medicines, were first classified in October 2004 as Class C Part III (partially exempted) controlled drugs, due to being the principal ingredient in methamphetamine.[53] New Zealand Customs and police officers continued to make large interceptions of precursor substances believed to be destined for methamphetamine production. On 9 October 2009, Prime Minister John Key announced pseudoephedrine-based cold and flu tablets would become prescription-only drugs and reclassified as a class B2 drug.[54] The law was amended by The Misuse of Drugs Amendment Bill 2010, which passed in August 2011.[55]

In the UK, pseudoephedrine is available over the counter under the supervision of a qualified pharmacist, or on prescription. In 2007, the MHRA reacted to concerns over diversion of ephedrine and pseudoephedrine for the illicit manufacture of methamphetamine by introducing voluntary restrictions limiting over the counter sales to one box containing no more than 720 mg of pseudoephedrine in total per transaction. These restrictions became law in April 2008.[57] However no form of ID is required.

Attempts to control the sale of the drug date back to 1986, when federal officials at the Drug Enforcement Administration (DEA) first drafted legislation, later proposed by Senator Bob Dole, R-KS, that would have placed a number of chemicals used in the manufacture of illicit drugs under the Controlled Substances Act. The bill would have required each transaction involving pseudoephedrine to be reported to the government, and federal approval of all imports and exports. Fearing this would limit legitimate use of the drug, lobbyists from over the counter drug manufacturing associations sought to stop this legislation from moving forward, and were successful in exempting from the regulations all chemicals that had been turned into a legal final product, such as Sudafed.[58]

Prior to the passage of the Combat Methamphetamine Epidemic Act of 2005, sales of the drug became increasingly regulated, as DEA regulators and pharmaceutical companies continued to fight for their respective positions. The DEA continued to make greater progress in their attempts to control pseudoephedrine as methamphetamine production skyrocketed, becoming a serious problem in the western United States. When purity dropped, so did the number of people in rehab and people admitted to emergency rooms with methamphetamine in their systems. However, this reduction in purity was usually short lived, as methamphetamine producers eventually found a way around the new regulations.[59]

Congress passed the Combat Methamphetamine Epidemic Act of 2005 ("CMEA") as an amendment to the renewal of the USA PATRIOT Act. Signed into law by president George W. Bush on March 6, 2006, the act amended 21 U.S.C.§ 830, concerning the sale of pseudoephedrine-containing products. The law mandated two phases, the first needing to be implemented by April 8, 2006, and the second to be completed by September 30, 2006. The first phase dealt primarily with implementing the new buying restrictions based on amount, while the second phase encompassed the requirements of storage, employee training, and record keeping.[60] Though the law was mainly directed at pseudoephedrine products it also applies to all over-the-counter products containing ephedrine, pseudoephedrine, and phenylpropanolamine, their salts, optical isomers, and salts of optical isomers.[60] Pseudoephedrine was defined as a "scheduled listed chemical product" under 21 U.S.C.§ 802(45(A)). The act included the following requirements for merchants ("regulated sellers") who sell such products:

Required a retrievable record of all purchases, identifying the name and address of each party, to be kept for two years

Required verification of proof of identity of all purchasers

Required protection and disclosure methods in the collection of personal information

Required reports to the Attorney General of any suspicious payments or disappearances of the regulated products

Required training of employees with regard to the requirements of the CMEA. Retailers must self-certify as to training and compliance.

The non-liquid dose form of regulated products may only be sold in unit dose blister packs

Regulated products must be stored behind the counter or in a locked cabinet in such a way as to restrict public access

Sales limits (per customer):

Daily sales limit—must not exceed 3.6 grams of pseudoephedrine base without regard to the number of transactions

30-day (not monthly) sales limit—must not exceed 7.5 grams of pseudoephedrine base if sold by mail order or "mobile retail vendor"

Oregon and Mississippi require a prescription for the purchase of products containing pseudoephedrine.[66][67] Oregon reduced the number of methamphetamine lab seizures from 467 in 2004 (the final full year before implementation of the prescription only law)[68] to a new low of 12 in 2009.[69] However, the decrease in meth lab incidents in Oregon occurred largely before the prescription-only law took effect, according to a NAMSDL report titled Pseudoephedrine Prescription Laws in Oregon and Mississippi[70]. The report posits that the decline in meth lab incidents in both states may be due to other factors: "Mexican traffickers may have contributed to the decline in meth labs in Mississippi and Oregon (and surrounding states) as they were able to provide ample supply of equal or greater quality meth at competitive prices". Additionally, similar decreases in meth lab incidents were seen in surrounding states, according to the report, and meth-related deaths in Oregon have dramatically risen since 2007. Some municipalities in Missouri have enacted similar ordinances, including Washington,[71] Union,[72] New Haven,[73] Cape Girardeau[74] and Ozark.[75] Certain pharmacies in Terre Haute, Indiana do so as well.[76]

Another approach to controlling the drug on the state level which has been mandated by some state governments to control the purchases of their citizens is the use of electronic tracking systems, which require the electronic submission of specified purchaser information by all retailers who sell pseudoephedrine. 32 states now require the National Precursor Log Exchange (NPLEx) to be used for every pseudoephedrine and ephedrine OTC purchase, and ten of the eleven largest pharmacy chains in the US voluntarily contribute all of their similar transactions to NPLEx. These states have seen dramatic results in reducing the number of methamphetamine laboratory seizures. Prior to implementation of the system in Tennessee in 2005, methamphetamine laboratory seizures totaled 1,497 in 2004, but were reduced to 955 in 2005, and 589 in 2009.[69] Kentucky's program was implemented statewide in 2008, and since statewide implementation, the number of laboratory seizures has significantly decreased.[69] Oklahoma initially experienced success with their tracking system after implementation in 2006, as the number of seizures dropped in that year and again in 2007. However, in 2008, seizures began rising again, and have continued to rise in 2009.[69] However, when Oklahoma adopted NPLEx, their lab seizures also dropped significantly.

NPLEx appears to be successful by requiring the real-time submission of transactions, thereby enabling the relevant laws to be enforced at the point of sale. By creating a multi-state database and the ability to compare all transactions quickly, NPLEx enables pharmacies to deny purchases that would be illegal based on gram limits, age, or even to convicted meth offenders in some states. NPLEx also enforces the federal gram limits across state lines, which was impossible with state-operated systems. Access to the records is by law enforcement agencies only, through an online secure portal.[77]

1.
Drug nomenclature
–
Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the drug. There are various systems of nomenclature and thus various chemical names for any one substance. The most important is the IUPAC name, chemical names are typically very long and too complex to be commonly used in referring to a drug. Sometimes, a company that is developing a drug might give the drug a company code, for example, CDP870 is UCB’s company code for Cimzia. Many of these codes, although not all, have prefixes that correspond to the company name, during development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, and it will apply for a generic name for that country. It will also apply for an International Nonproprietary Name through the World Health Organization, nowadays the national nonproprietary names are usually the same as the INN. The generic names usually indicate via their stems what drug class the drug belongs to, for example, one can tell that aciclovir is an antiviral drug because its name ends in the -vir suffix. Otherwise the 2 names are both given, joined by hyphens or slashes. For example, suspensions combining trimethoprim and sulfamethoxazole are called either trimethoprim/sulfamethoxazole or co-trimoxazole, similarly, co-codamol is codeine-acetaminophen, and co-triamterzide is triamterene-hydrochlorothiazide. The USP ceased maintaining PENs, but the similar co-prefixed BANs are still current, for drugs that make it all the way through development, testing, and regulatory acceptance, the pharmaceutical company then gives the drug a trade name. The term trade name is a term in the pharmaceutical industry for a brand name or trademark name. For example, Lipitor is Pfizers trade name for atorvastatin, a cholesterol-lowering medication, Drug names are often subject to legal regulation, including approval for new drugs and on packaging to establish clear rules about adulterants and fraudulent or misleading labelling. A national formulary is often designated to define drug names for regulatory purposes, unbiased mentions of a drug place the nonproprietary name first and follow it with the trade name in parentheses, if relevant. This pattern is important for the literature, where conflict of interest is disclosed or avoided. The authors reporting on a study are not endorsing any particular brand of drug and they will often state which brand was used, for methodologic validity, but they do so in a way that makes clear the absence of endorsement. For example, the 2015 American Society of Hematology publication policies say, Non-proprietary names should be used and he first letter of the name of a proprietary drug should be capitalized

2.
Drugs.com
–
Drugs. com is an online pharmaceutical encyclopedia which provides drug information for consumers and healthcare professionals primarily in the USA. The domain Drugs. com was registered by Bonnie Neubeck in 1994. In 1999 at the height of the boom, Eric MacIver purchased an option to buy the domain from Neubeck. com. Venture Frogs sold the drugs. com domain name to an investor in June 2001. The Drugs. com website is owned and operated by the Drugsite Trust, the Drugsite Trust is a privately held Trust administered by two New Zealand pharmacists, Karen Ann and Phillip James Thornton The Drugs. com website was officially launched in September 2001. Stedmans, AHFS, Harvard Health Publications, Mayoclinic, North American Compendiums, in March 2008, Drugs. com announced the release of Mednotes —an online personal medication record application which connected to Google Health. In May 2010, U. S. FDA announced a collaboration with Drugs. com to distribute consumer health updates on the Drugs. com website, Drugs. com is certified by the TRUSTe online privacy certification program and the HONcode Health on the Net Foundation

3.
Regulation of therapeutic goods
–
The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc

4.
European Medicines Agency
–
The European Medicines Agency is a European Union agency for the evaluation of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products, roughly parallel to the drug part of the U. S. The EU is currently the source of about one-third of the new drugs brought onto the market each year. After the United Kingdom withdrawal from the European Union referendum the agency is preparing to relocate, more specifically, it coordinates the evaluation and monitoring of centrally authorised products and national referrals, developing technical guidance and providing scientific advice to sponsors. Its scope of operations is medicinal products for human and veterinary use including biologics and advanced therapies, the agency is composed of the Secretariat, a management board, seven scientific committees and a number of scientific working parties. The Management Board provides administrative oversight to the Agency, including approval of budgets and plans, the Agency decentralises its scientific assessment of medicines by working through a network of about 4500 experts throughout the EU. The EMA draws on resources of over 40 National Competent Authorities of EU Member states, the centralised procedure is also open to products that bring a significant therapeutic, scientific or technical innovation, or is in any other respect in the interest of patient or animal health. As a result, the majority of genuinely novel medicines are authorised through the EMA, for products eligible for or requiring centralised approval, a company submits an application for a marketing authorisation to the EMA. A single evaluation is carried out through the Committee for Medicinal Products for Human Use, if the Committee concludes that the quality, safety and efficacy of the medicinal product is sufficiently proven, it adopts a positive opinion. This is sent to the European Commission to be transformed into a marketing authorisation valid for the whole of the EU, a special type of approval is the paediatric-use marketing authorisation, which can be granted for medical products intended exclusively for paediatric use. The CHMP is obliged by the regulation to reach decisions within 210 days and this compares well with the average of 500 days taken by the U. S. Food and Drug Administration. The Committee for Medicinal Products for Veterinary Use operates in analogy to the CHMP as described above, the Committee on Orphan Medicinal Products administers the granting of orphan drug status since 2000. The COMP evaluates the application and makes a recommendation for the designation which is granted by the European Commission. The Paediatric Committee deals with the implementation of the legislation in Europe Regulation No 1901/2006 since 2007. It assesses the quality, safety and efficacy of ATMPs, a seventh committee, the Pharmacovigilance Risk Assessment Committee has come into function in 2012 with the implementation of the new EU pharmacovigilance legislation. Referrals The Agency coordinates arbitration procedures relating to medicinal products that are approved or under consideration by Member States in non-centralized authorisation procedures, telematics projects The Agency is responsible for implementing a central set of pan-European systems and databases such as EudraVigilance, EudraCT and EudraPharm. Following the decision of the United Kingdom to vote to leave the European Union, according to EU Law the European Commission will need to decide the criteria surrounding the fate of the EMAs location. The heads of state will then meet to vote on their preferred successor, the EUs Health Commissioner Vytenis Andriukaitis has said in the past that the preferred choice would be a location where an easy set up and guarantee of smooth operations would be available

5.
Pharmacy medicines
–
A prescription drug is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription, the reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient education. Different jurisdictions have different definitions of what constitutes a prescription drug, rx is often used as a short form for prescription drug in North America- a contraction of the Latin word recipe meaning take. Prescription drugs are often dispensed together with a monograph that gives detailed information about the drug, the use of prescription drugs has been increasing since the 1960s. In the U. S. 88% of older adults use at least 1 prescription drug, who is able to prescribe the drug. When purchasing a drug under the PBS the maximum price a consumer pays is the patient co-payment contribution and those covered by government entitlements and those covered under the Repatriation Pharmaceutical Benefits Scheme have a reduced co-payment, which is $6.00 in 2014. The table below indicates the changes in co-payments over the years and these co-payments are compulsory and cannot be discounted by pharmacies under any circumstances. Private prescriptions are issued for medicines not covered on the PBS, or being used off-label, the patient pays the pharmacy for medicines privately prescribed. In the United Kingdom the Medicines Act 1968 and Prescription Only Medicines Order 1997 contain regulations that cover the supply of sale, use, prescribing is also covered by this legislation. A patient visits a medical practitioner or dentist authorised to prescribe drugs and certain other medical items, also, suitably qualified and experienced nurses and pharmacists may be independent prescribers. Both can prescribe all POMs but pharmacists are not allowed to prescribe schedule 1 controlled drugs, once issued, a prescription is taken by the patient to a pharmacy, which dispenses the medicine. Most prescriptions in the UK are NHS prescriptions, subject to a standard charge unrelated to what is dispensed, the NHS prescription fee was increased to £8. The pharmacy charges the NHS the actual cost of the medicine, a patient can consolidate prescription charges using a prescription payment certificate, effectively capping costs at £29.10 per quarter or £104.00 per year. Outside the NHS, private prescriptions are issued by private medical practitioners, NHS supply beyond three months worth is not covered, and must be purchased privately. A patient pays the pharmacy the normal price for medicine prescribed outside the NHS, in the United States, the Federal Food, Drug, and Cosmetic Act defines what substances require a prescription in order to be dispensed by a pharmacy. The Controlled Substances Act was enacted into law by the Congress of the United States in 1970, the CSA is the federal U. S. drug law under which the manufacture, importation, possession, use and distribution of certain substances is regulated. The legislation created five schedules with varying qualifications for a substance to be included in each, the safety and effectiveness of prescription drugs in the US is regulated by the federal Prescription Drug Marketing Act of 1987. The Food and Drug Administration is charged with implementing this law, misuse or abuse of prescription drugs can lead to adverse drug events, including those due to dangerous drug interactions

6.
Mississippi
–
Mississippi /ˌmɪsᵻˈsɪpi/ is a state in the southern region of the United States, with part of its southern border formed by the Gulf of Mexico. Its western border is formed by the Mississippi River, the state has a population of approximately 3 million. It is the 32nd most extensive and the 32nd most populous of the 50 United States, located in the center of the state, Jackson is the state capital and largest city, with a population of approximately 175,000 people. The state is heavily forested outside of the Mississippi Delta area, before the American Civil War, most development in the state was along riverfronts, where slaves worked on cotton plantations. After the war, the bottomlands to the interior were cleared, by the end of the 19th century, African Americans made up two-thirds of the Deltas property owners, but timber and railroad companies acquired much of the land after a financial crisis. Clearing altered the Deltas ecology, increasing the severity of flooding along the Mississippi, much land is now held by agribusinesses. The states catfish aquaculture farms produce the majority of farm-raised catfish consumed in the United States, since the 1930s and the Great Migration, Mississippi has been majority white, albeit with the highest percentage of black residents of any U. S. state. From the early 19th century to the 1930s, its residents were mostly black, whites retained political power through Jim Crow laws. In 2010, 37% of Mississippians were African Americans, the highest percentage of African Americans in any U. S. state, since gaining enforcement of their voting franchise in the late 1960s, most African Americans support Democratic candidates in local, state and national elections. Conservative whites have shifted to the Republican Party, African Americans are a majority in many counties of the Mississippi-Yazoo Delta, an area of historic settlement during the plantation era. Since 2011 Mississippi has been ranked as the most religious state in the country, the states name is derived from the Mississippi River, which flows along its western boundary. Settlers named it after the Ojibwe word misi-ziibi, in addition to its namesake, major rivers in Mississippi include the Big Black River, the Pearl River, the Yazoo River, the Pascagoula River, and the Tombigbee River. Major lakes include Ross Barnett Reservoir, Arkabutla Lake, Sardis Lake, Mississippi is entirely composed of lowlands, the highest point being Woodall Mountain, in the foothills of the Cumberland Mountains,807 feet above sea level. The lowest point is sea level at the Gulf coast, the states mean elevation is 300 feet above sea level. Most of Mississippi is part of the East Gulf Coastal Plain, the coastal plain is generally composed of low hills, such as the Pine Hills in the south and the North Central Hills. The Pontotoc Ridge and the Fall Line Hills in the northeast have somewhat higher elevations, yellow-brown loess soil is found in the western parts of the state. The northeast is a region of black earth that extends into the Alabama Black Belt. The coastline includes large bays at Bay St. Louis, Biloxi, the northwest remainder of the state consists of the Mississippi Delta, a section of the Mississippi Alluvial Plain

7.
Pharmacokinetics
–
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism

8.
Bioavailability
–
By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient, Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. Bioavailability is defined differently for drugs as opposed to dietary supplements primarily due to the method of administration and Food. Bioaccessibility is a related to bioavailability in the context of biodegradation. A molecule is said to be bioaccessible when is available to cross a cellular membrane from the environment. In pharmacology, bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action and it is denoted by the letter f. Therefore, bioavailability for dietary supplements can be defined as the proportion of the administered substance capable of being absorbed, in both pharmacology and nutrition sciences, bioavailability is measured by calculating the area under curve of the drug concentration time profile. Bioavailability is commonly a factor in the production of crops. Toxic materials in soil, such as lead from paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess and it is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be normalized, consequently, the amount absorbed is corrected by dividing the corresponding dose administered. The absolute bioavailability is the area under curve non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the route is given below. If we compare the two different dosage forms having same active ingredients and compare the two drug bioavailability is called comparative bioavailability, although knowing the true extent of systemic absorption is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires a reference, that is. These limitations may be overcome, however, by administering a low dose of an isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be administered with a minimum of toxicology, the technique was first applied using stable-isotopes such as 13C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, 14C labelled drugs are administered intravenously and accelerator mass spectrometry used to measure the isotopically labelled drug along with mass spectrometry for the unlabelled drug, in all such cases, to conduct an absolute bioavailability study requires that the drug be given intravenously. Intravenous administration of a drug can provide valuable information on the fundamental pharmacokinetic parameters of volume of distribution

9.
Drug metabolism
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Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. These pathways are a form of biotransformation present in all groups of organisms. These reactions often act to detoxify poisonous compounds, the study of drug metabolism is called pharmacokinetics. The metabolism of drugs is an important aspect of pharmacology. For example, the rate of metabolism determines the duration and intensity of a drugs pharmacologic action, the enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also important in agriculture, since they may produce resistance to pesticides and herbicides. Drug metabolism is divided into three phases, in phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are conjugated to polar compounds in phase II reactions. These reactions are catalysed by enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be processed, before being recognised by efflux transporters. Drug metabolism often converts lipophilic compounds into hydrophilic products that are readily excreted. The exact compounds an organism is exposed to will be unpredictable, and may differ widely over time. The solution that has evolved to address this problem is an elegant combination of physical barriers, all organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. This selective uptake means that most hydrophilic molecules cannot enter cells, in contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid-soluble xenobiotics using membrane barriers. However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics and these systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general one or more charged groups. However, since these compounds are few in number, specific enzymes can recognize, the metabolism of xenobiotics is often divided into three phases, - modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells, in phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system and these enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates

10.
Excretion
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Excretion is the process by which metabolic wastes and other non-useful materials are eliminated from an organism. In vertebrates this is carried out by the lungs, kidneys. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell, excretion is an essential process in all forms of life. For example, in urine is expelled through the urethra. In unicellular organisms, waste products are discharged directly through the surface of the cell, green plants produce carbon dioxide and water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis, oxygen is a by product generated during photosynthesis, and exits through stomata, root cell walls, and other routes. Plants can get rid of water by transpiration and guttation. These latter processes do not need added energy, they act passively, however, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants also excrete some waste substances into the soil around them, in animals, the main excretory products are carbon dioxide, ammonia, urea, uric acid, guanine and creatine. The liver and kidneys clear many substances from the blood, aquatic animals usually excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution. In terrestrial animals ammonia-like compounds are converted into other materials as there is less water in the environment. Birds excrete their nitrogenous wastes as uric acid in the form of a paste and this is metabolically more expensive, but allows more efficient water retention and it can be stored more easily in the egg. Many avian species, especially seabirds, can also excrete salt via specialized nasal salt glands, in insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is actively transported into the tubule, which transports the wastes to the intestines, the metabolic waste is then released from the body along with fecal matter. The excreted material may be called dejecta or ejecta, in pathology the word ejecta is more commonly used. UAlberta. ca, Animation of excretion Brian J Ford on leaf fall in Nature

11.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service

12.
DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result, links to DrugBank are maintained for nearly all drugs listed in Wikipedia, DrugBank is widely used by the drug industry, medicinal chemists, pharmacists, physicians, students and the general public. Its extensive drug and drug-target data has enabled the discovery and repurposing of a number of existing drugs to treat rare, the latest release of the database contains 8227 drug entries including 2003 FDA-approved small molecule drugs,221 FDA-approved biotech drugs,93 nutraceuticals and over 6000 experimental drugs. Additionally,4270 non-redundant protein sequences are linked to these drug entries, each DrugCard entry contains more than 200 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Four additional databases, HMDB, T3DB, SMPDB and FooDB are also part of a suite of metabolomic/cheminformatic databases. The first version of DrugBank was released in 2006 and this early release contained relatively modest information about 841 FDA-approved small molecule drugs and 113 biotech drugs. It also included information on 2133 drug targets, the second version of DrugBank was released in 2009. This greatly expanded and improved version of the database included 1344 approved small molecule drugs and 123 biotech drugs as well as 3037 unique drug targets. Version 2.0 also included, for the first time, withdrawn drugs and illicit drugs, version 3.0 was released in 2011. This version contained 1424 approved small molecule drugs and 132 biotech drugs as well as >4000 unique drug targets, version 3.0 also included drug transporter data, drug pathway data, drug pricing, patent and manufacturing data as well as data on >5000 experimental drugs. Version 4.0 was released in 2014 and this version included 1558 FDA-approved small molecule drugs,155 biotech drugs and 4200 unique drug targets. Version 4.0 also incorporated information on drug metabolites, drug taxonomy, drug spectra, drug binding constants. Table 1 provides a complete statistical summary of the history of DrugBank’s development. All data in DrugBank is non-proprietary or is derived from a non-proprietary source and it is freely accessible and available to anyone. In addition, nearly every item is fully traceable and explicitly referenced to the original source. DrugBank data is available through a web interface and downloads

13.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses

14.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets

15.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH

16.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES

17.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure

18.
Sympathomimetic
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Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. The primary endogenous agonists of the nervous system are the catecholamines. Sympathomimetic drugs are used to treat cardiac arrest and low pressure, or even delay premature labor. If the amine is primary or secondary, it will have direct action, also, if the amine has bulky substituents, then it will have greater beta adrenergic receptor activity, but if the substituent is not bulky, then it will favor the alpha adrenergic receptors. Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects, salbutamol is a widely used direct-acting β2-agonist. Other examples include phenylephrine, isoproterenol, and dobutamine, stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam is used intravenously to treat hypertensive crisis. Dopaminergic stimulants such as amphetamine, ephedrine, and propylhexedrine work by causing the release of dopamine and norepinephrine, a primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity. The pKa of the amine is approximately 8. 5-10, the presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha- and beta-adrenergic activity. Substances such as cocaine also affect dopamine, and some such as MDMA affect serotonin. Norepinephrine is synthesized by the body from the amino acid tyrosine, and is used in the synthesis of epinephrine, thus, all sympathomimetic amines fall into the larger group of stimulants. Physical withdrawal from some sedatives can be lethal, for instance benzodiazepine withdrawal syndrome. Parasympatholytic and sympathomimetic have similar effects, but through different pathways. For example, both cause mydriasis, but parasympatholytics reduce accommodation while sympathomimetics do not

19.
Substituted phenethylamine
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The structural formula of any substituted phenethylamine contains a phenyl ring that is joined to an amino group via an ethyl sidechain. Hence, any substituted phenethylamine can be classified according to the substitution of hydrogen atoms on phenethylamines phenyl ring, sidechain, numerous endogenous compounds – including hormones, monoamine neurotransmitters, and many trace amines – are substituted phenethylamines. Several notable recreational drugs, such as MDMA, methamphetamine, all of the substituted amphetamines and substituted methylenedioxyphenethylamines are substituted phenethylamines as well. Substituted amphetamines Substituted methylenedioxyphenethylamines Substituted cathinones Substituted phenylmorpholines 2Cs and DOx Substituted tryptamines

20.
Substituted amphetamine
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The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Some of amphetamines substituted derivatives occur in nature, for example in the leaves of Ephedra and these have been used since antiquity for their pharmacological effects. Amphetamine was first produced at the end of the 19th century, by the 1930s, amphetamine and some of its derivative compounds found use as decongestants in the symptomatic treatment of colds and also occasionally as psychoactive agents. Their effects on the nervous system are diverse, but can be summarized by three overlapping types of activity, psychoanaleptic, hallucinogenic and empathogenic. Various substituted amphetamines may cause these actions either separately or in combination, amphetamines are a subgroup of the substituted phenethylamine class of compounds. Substitution of hydrogen results in a large class of compounds. Natives of Yemen and Ethiopia have a tradition of chewing khat leaves to achieve a stimulating effect. The active substances of khat are cathinone and, to a lesser extent, amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu, although its pharmacological effects remained unknown until the 1930s. MDMA was produced in 1912 as an intermediate product, however, this synthesis also went largely unnoticed. In the 1920s, both methamphetamine and the dextrorotatory optical isomer of amphetamine, dextroamphetamine, were synthesized and this synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat asthma extracted exclusively from natural sources. Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French, as a medicine for colds and nasal congestion. Subsequently, amphetamine was used in the treatment of narcolepsy, obesity, hay fever, orthostatic hypotension, epilepsy, Parkinsons disease, alcoholism, the reinforcing effects of substituted amphetamines were quickly discovered, and the misuse of substituted amphetamines had been noted as far back as 1936. During World War II, amphetamines were used by the German military to keep their tank crews awake for long periods and it was noticed that extended rest was required after such artificially induced activity. The widespread use of substituted amphetamines began in postwar Japan and quickly spread to other countries, modified designer amphetamines gained popularity since the 1960s, such as MDA and PMA. In 1970, the United States adopted the Controlled Substances Act that limited non-medical use of substituted amphetamines, street use of PMA was noted in 1972. MDMA emerged as a substitute to MDA in the early 1970s, american chemist Alexander Shulgin first synthesized the drug in 1976 and through him the drug was briefly introduced into psychotherapy. Recreational use grew and in 1985 MDMA was banned by the US authorities in an emergency scheduling initiated by the Drug Enforcement Administration, since the mid-1990s, MDMA has become a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as ecstasy. Ongoing trials are investigating its efficacy as an adjunct to psychotherapy in the management of treatment-resistant post-traumatic stress disorder

21.
Stimulant
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Stimulants is an overarching term that covers many drugs including those that increase activity of the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Due to their rendering a characteristic up feeling, stimulants are also referred to as uppers. Depressants or downers, which decrease mental and/or physical function, are in stark contrast to stimulants and are considered to be the functionally opposite drug class, Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate and it is estimated that the percent of the population that has abused amphetamines, cocaine and MDMA combined is between. 8% and 2. 1%. Stimulants in therapeutic doses, such as given to patients with ADHD, increases ability to focus, vigor, sociability, libido. However, in higher doses stimulants may actually decrease the ability to focus, in higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep. Many, but not all, stimulants have ergogenic effects, Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while drugs such as cocaine and methamphetamine have the opposite effect. In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia, most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to such as mydriasis, increased heart rate, blood pressure, respiratory rate. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, however given the complexity of the mechanisms that underly these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal. Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, a review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer term studies. A review of a long period of prescription stimulate use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, Abuse of prescription stimulants or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of disease, stroke. Cocaine may also increase risk for disease, as well as damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, Drugs used to treat sleep disorders such as excessive daytime sleepiness are called eugeroics, and include notable stimulants such as modafinil

22.
Salt (chemistry)
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In chemistry, a salt is an ionic compound that results from the neutralization reaction of an acid and a base. Salts are composed of related numbers of cations and anions so that the product is electrically neutral and these component ions can be inorganic, such as chloride, or organic, such as acetate, and can be monatomic, such as fluoride, or polyatomic, such as sulfate. There are several varieties of salts, salts that hydrolyze to produce hydroxide ions when dissolved in water are alkali salts, whilst those that hydrolyze to produce hydronium ions in water are acidic salts. Neutral salts are those salts that are neither acidic nor basic, zwitterions contain an anionic centre and a cationic centre in the same molecule, but are not considered to be salts. Examples of zwitterions include amino acids, many metabolites, peptides, usually, non-dissolved salts at standard conditions for temperature and pressure are solid, but there are exceptions. Molten salts and solutions containing dissolved salts are called electrolytes, as they are able to conduct electricity. As observed in the cytoplasm of cells, in blood, urine, plant saps and mineral waters, therefore, their salt content is given for the respective ions. Salts can appear to be clear and transparent, opaque, and even metallic, in many cases, the apparent opacity or transparency are only related to the difference in size of the individual monocrystals. Since light reflects from the boundaries, larger crystals tend to be transparent. The color of the salt is due to the electronic structure in the d-orbitals of transition elements or in the conjugated organic dye framework. Different salts can elicit all five basic tastes, e. g. salty, sweet, sour, bitter, and umami or savory. Salts of strong acids and strong bases are non-volatile and odorless and that slow, partial decomposition is usually accelerated by the presence of water, since hydrolysis is the other half of the reversible reaction equation of formation of weak salts. Many ionic compounds can be dissolved in water or other similar solvents, the exact combination of ions involved makes each compound have a unique solubility in any solvent. The solubility is dependent on how well each ion interacts with the solvent, for example, all salts of sodium, potassium and ammonium are soluble in water, as are all nitrates and many sulfates – barium sulfate, calcium sulfate and lead sulfate are examples of exceptions. However, ions that bind tightly to each other and form highly stable lattices are less soluble, for example, most carbonate salts are not soluble in water, such as lead carbonate and barium carbonate. Some soluble carbonate salts are, sodium carbonate, potassium carbonate, solid salts do not conduct electricity. Moreover, solutions of salts also conduct electricity, the name of a salt starts with the name of the cation followed by the name of the anion. Salts are often referred to only by the name of the cation or by the name of the anion. g

23.
Over-the-counter drug
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In many countries, OTC drugs are selected by a regulatory agency to ensure that they are ingredients that are safe and effective when used without a physicians care. OTC drugs are regulated by active pharmaceutical ingredients, not final products. By regulating APIs instead of specific drug formulations, governments allow manufacturers freedom to formulate ingredients, or combinations of ingredients, into proprietary mixtures. The term over-the-counter may be somewhat counterintuitive, since, in many countries, in contrast, prescription drugs are almost always passed over a counter from the pharmacist to the customer. Some drugs may be classified as over-the-counter, but may only be dispensed by a pharmacist after an assessment of the patients needs or the provision of patient education. In many countries, a number of OTC drugs are available in establishments without a pharmacy, such as stores, supermarkets. Regulations detailing the establishments where drugs may be sold, who is authorized to dispense them, as of 2011, around a third of older adults in the U. S. reportedly use OTC drugs. In Canada, there are four drug schedules, Schedule 1, Schedule 2, Do not require a prescription, but require an assessment by a pharmacist prior to sale. These drugs are kept in an area of the pharmacy where there is no public access, Schedule 3, Do not require a prescription, but must be kept in an area under the supervision of a pharmacist. These drugs are kept in an area of the outlet where self-selection is possible. Unscheduled, Do not require a prescription and may be sold in any retail outlet, all medications outside of Schedule 1 may be considered an OTC drug, as they do not require prescriptions for sale. While the National Association of Pharmacy Regulatory Authorities provides recommendations on the scheduling of drugs for sale in Canada, due to this, the exact drugs found in each schedule may vary from province to province. The drug can be on the shelves like any other product, examples are domperidone,400 mg ibuprofen up to 50 tablets and dextromethorphan. The drugs are usually on the shelves and the store sells items like toys, gadgets, perfumes. The drugs in this category have limited risk and addiction potential, examples are naproxen and diclofenac in small amounts, cinnarizine,400 mg ibuprofen up to 20 tablets and also 500 mg paracetamol up to 50 tablets. In the United States, the manufacture and sale of OTC substances is regulated by the Food, the FDA requires that all new drugs obtain a New Drug Application before entering interstate commerce, but the act exempts any drugs generally recognized as safe and effective from this requirement. Thus, in the United States an OTC drug product is allowed to be marketed either pursuant to an FDA monograph, the Federal Trade Commission regulates advertising of OTC products. This is in contrast to prescription drug advertising, which is regulated by the FDA, the FDA requires that OTC products are labeled with an approved Drug Facts label to educate consumers about their medications

Drug nomenclature
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Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the

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Regulation of therapeutic goods in the United States

Drugs.com
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Drugs. com is an online pharmaceutical encyclopedia which provides drug information for consumers and healthcare professionals primarily in the USA. The domain Drugs. com was registered by Bonnie Neubeck in 1994. In 1999 at the height of the boom, Eric MacIver purchased an option to buy the domain from Neubeck. com. Venture Frogs sold the drugs. co

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Drugs.com

Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of

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Methylphenidate, in the form of Ritalin pills.

European Medicines Agency
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The European Medicines Agency is a European Union agency for the evaluation of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products, roughly parallel to the drug part of the U. S. The EU is currently the source of about one-third of the new drugs brought onto the market each year. After the

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European Medicines Agency

Pharmacy medicines
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A prescription drug is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription, the reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient e

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Regulation of therapeutic goods in the United States

Mississippi
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Mississippi /ˌmɪsᵻˈsɪpi/ is a state in the southern region of the United States, with part of its southern border formed by the Gulf of Mexico. Its western border is formed by the Mississippi River, the state has a population of approximately 3 million. It is the 32nd most extensive and the 32nd most populous of the 50 United States, located in the

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Flag

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Bottomland hardwood swamp near Ashland, Mississippi

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Jackson, Mississippi

Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and

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Different forms of tablets, which will have different pharmacokinetic behaviours after their administration.

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Graph that demonstrates the Michaelis-Menten kinetics model for the relationship between an enzyme and a substrate: one of the parameters studies in pharmacokinetics, where the substrate is a pharmaceutical drug.

Bioavailability
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By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient, Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculati

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Absolute bioavailability is a ratio of areas under the curves. IV, intravenous; PO, oral route.

Drug metabolism
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Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. These pathways are a form of biotransformation present in all groups of organisms. These reactions often act to detoxify poisonous compounds, the study of drug metabolism is called pharmacokinetics. The metabolism of drugs is an i

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Cytochrome P450 oxidases are important enzymes in xenobiotic metabolism.

Excretion
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Excretion is the process by which metabolic wastes and other non-useful materials are eliminated from an organism. In vertebrates this is carried out by the lungs, kidneys. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell, excretion is an essential process in all forms of life. For example, in u

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White cast of uric acid defecated with the dark feces from a lizard. Insects, birds and some other reptiles also undergo a similar mechanism.

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Chemical structure of uric acid.

PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be dow

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PubChem

DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result

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Fig. 1. DrugBank DrugCard

ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The

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ChemSpider

ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company

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Centres and institutes

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ChEMBL

Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of

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Al 2 (SO 4) 3

Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specifi

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Generation of SMILES: Break cycles, then write as branches off a main backbone. (Ciprofloxacin)

International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL lic

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L - ascorbic acid

Sympathomimetic
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Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. The primary endogenous agonists of the nervous system are the catecholamines. Sympathomimetic drugs are used to treat cardiac arrest and low pressure, or even delay premature labor. If the amine is primary or secondary, it

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Epinephrine

Substituted phenethylamine
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The structural formula of any substituted phenethylamine contains a phenyl ring that is joined to an amino group via an ethyl sidechain. Hence, any substituted phenethylamine can be classified according to the substitution of hydrogen atoms on phenethylamines phenyl ring, sidechain, numerous endogenous compounds – including hormones, monoamine neur

Substituted amphetamine
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The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Some of amphetamines substituted derivatives occur in nature, for example in the leaves of Ephedra and these have been used since antiquity for their pharmacological effects. Amphetamine was first produced at

Stimulant
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Stimulants is an overarching term that covers many drugs including those that increase activity of the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Due to their rendering a characteristic up feeling, stimulants are also referred to as uppers. Depressants or downers, which decrease mental and/or phys

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Ritalin sustained-release (SR) 20 mg tablets

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Roasted coffee beans, a common source of caffeine.

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Illicit tablets containing MDMA

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Catha edulis

Salt (chemistry)
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In chemistry, a salt is an ionic compound that results from the neutralization reaction of an acid and a base. Salts are composed of related numbers of cations and anions so that the product is electrically neutral and these component ions can be inorganic, such as chloride, or organic, such as acetate, and can be monatomic, such as fluoride, or po

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The salt copper(II) sulfate as the mineral chalcanthite.

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Potassium dichromate, a bright orange salt used as a pigment.

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Solid lead(II) sulfate (PbSO 4)

Over-the-counter drug
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In many countries, OTC drugs are selected by a regulatory agency to ensure that they are ingredients that are safe and effective when used without a physicians care. OTC drugs are regulated by active pharmaceutical ingredients, not final products. By regulating APIs instead of specific drug formulations, governments allow manufacturers freedom to f

2.
Sodium and fluorine bonding ionically to form sodium fluoride. Sodium loses its outer electron to give it a stable electron configuration, and this electron enters the fluorine atom exothermically. The oppositely charged ions are then attracted to each other. The sodium is oxidized, and the fluorine is reduced.

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Yinxu, ruins of an ancient palace dating from the Shang Dynasty (14th century BCE)

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Flag

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Some of the thousands of life-size Terracotta Warriors of the Qin Dynasty, c. 210 BCE

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The Great Wall of China was built by several dynasties over two thousand years to protect the sedentary agricultural regions of the Chinese interior from incursions by nomadic pastoralists of the northern steppes.